Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease

Official title

A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)

Overview

This is a 2-year follow-up study of a cohort of 35 CMT1A patients and 20 healthy volunteers. The main objective is identifying prognostic markers for CMT1A using multi-omics analysis. The study is recruiting subjects between the ages of 10 and 30. The most common inherited neuropathy is Charcot-Marie-Tooth disease type 1A (CMT1A), caused by a duplication of the gene expressing PMP22. CMT1A patients develop symptoms in early childhood with variable progression and there is no established therapy until now. Therapy must start in childhood, before peripheral nerves degenerate. However, we lack easily obtainable biomarkers in early disease stages. In CMT-MODs, we will identify disease and prognostic biomarkers in young CMT1A patients.

Detailed description

The CMT-MODs project aims to conduct a multi-omics analysis (transcriptomics, proteomics, lipidomics) in young patients with early-stage CMT1A. This evaluation should enable the identification of prognostic and change-sensitive biomarkers for use in clinical trials.

A large cohort of CMT1A children, adolescents and young adults aged 10-30 years over 12 months applying the novel clinical outcome measures CMT Examination Score/CMT Neuropathy Score Version Version 2 Rasch versions (CMTES-R/CMTNSv2-R), the functional outcome measure CMT-FOM, pCMT-Qol, as well as a nerve conduction study (NCS) and quantitative MRI will be assessed.

Blood (and optional skin) samples will be taken and gene expression of the most promising candidates will be identified.

This assessment of CMT patients at early disease stages will allow CMT-MODs to establish biomarkers that may serve as a standard readout for disease severity and predict the disease course.

Interventions

• Other Quantitative neuromuscular MRI
  Quantification of biomarkers as fat fraction, magnetization Transfer Ratio, muscular volume, relaxation time T2
• Other Skin biopsy
  Performed on the arm or index finger, depending on patient age
• Other Clinical scores
  ONLS, CMTES-R, CMT-Peds, CMT-FOM
• Other Blood test
  10 ml sample
• Other Patient Report Outcomes Measures
  pCMT-QoL, EVA, WALK-12, PGI-c, SF-12

Primary outcome measures

• Transcriptomic analysis [Time frame: Between inclusion (month 0) and one year later (month 12)]
• Proteomic analysis [Time frame: Between inclusion (month 0) and one year later (month 12)]

Secondary outcome measures (12)

• MRI muscle biomarkers : Fat Fraction measure [Time frame: Between inclusion (month 0) and one year later (month12)]
• MRI muscle biomarkers : Magnetization Transfer Ratio [Time frame: Between inclusion (month 0) and one year later (month12)]
• MRI muscle biomarkers : T2 relaxation time [Time frame: Between inclusion (month 0) and one year later (month12)]
• MRI muscle biomarkers : muscle volume [Time frame: Between inclusion (month 0) and one year later (month12)]
• Clinical score : ONLS [Time frame: Between inclusion (month 0) and one year later (month12)]
• Clinical score : CMTES-R [Time frame: Between inclusion (month 0) and one year later (month12)]
• Clinical score : CMT-FOM [Time frame: Between inclusion (month 0) and one year later (month12)]
• Clinical score : CMT-Peds [Time frame: Between inclusion (month 0) and one year later (month 12)]
• PROM (Patient Reported Outcomes Measures) : pCMT-QoL [Time frame: Between inclusion (month 0), month 6, and one year later (month12)]
• PROM (Patient Reported Outcomes Measures) : VAS [Time frame: Between inclusion (month 0), month 6, and one year later (month 12)]
• PROM (Patient Reported Outcomes Measures) : WALK-12 [Time frame: Between inclusion (month 0), month 6, and one year later (month 12)]
• PROM (Patient Reported Outcomes Measures) : PGI-c [Time frame: Between inclusion (month), month 6, and one year later (month 12)]

Eligibility criteria

Inclusion criteria

• Healthy volunteer or patient who has given consent for participation in the study or, for minors, a healthy volunteer whose two parents have given consent for participation in the study.
• Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed
• Patient able to walk with or without assistance

Exclusion criteria

• Healthy volunteer with neurological disorders
• Healthy volunteer or patient with a contraindication to MRI,
• Healthy volunteers or patient under 30 kg
• Helathy volunteer on long-term therapy
• Patient with other neuromuscular pathologies
• Patient in a period of exclusion from another research protocol at the time of signing the consent/non-opposition form
• Pregnant or breast-feeding women
• Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women)
• Subjects who cannot read and understand the French language well enough to be able to give their consent to participate in research

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Assistance Publique - Hôpitaux de Marseille — Marseille

Identifiers

NCT: NCT07049588 · RCAPHM24_0381 · 2024-A02403-44

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗